The development of catalytic molecular transformations based on multidentate activation of carboxy groups

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16315
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Osaka Prefecture University
• Principal Investigator: Kenichi Michigami 大阪府立大学, 理学(系)研究科(研究院), 助教 (20838742)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アミド / ペプチド / ジボリルアルカン / 有機触媒 / 脱水縮合

Outline of Final Research Achievements

Organoboron compounds have attracted significant attention as clean, water-releasing amide condensation catalysts, providing an opportunity of efficient synthesis of bioactive amides and peptides. We found "gem-diboronic acid", bearing two boronic acids onto one carbon atom, efficiently catalyzed dehydrative coupling of α-amino acids and peptide fragments, which are quite difficult with conventional arylboronic acid catalysts. Since gem-diboronic acid catalytic system can tolerate various functional groups within amino acids, the application to the synthesis of complex polypeptides is thus expected. We also developed new gem-diboronic acid derivatives enabling the catalytic functionalization of gem-diborylalkanes without C-B bond cleavage, which is not accessible by the precedent method. The protocol might thereby useful for structural modification of gem-diboronic acid catalysts.

Free Research Field

有機化学

Academic Significance and Societal Importance of the Research Achievements

芳香族ボロン酸は水のみを排出しつつアミド縮合を触媒するため、化学量論量の試薬が不要かつクリーンな有機触媒として大きな注目を集めてきた。しかし、芳香族ボロン酸はアミノ酸同士の縮合に対する触媒活性が著しく低い。筆者はgem-ジボロン酸がアミノ酸やペプチドフラグメントを触媒的にカップリングできることを報告した。本触媒は構造修飾の余地を残しているため、さらなる高活性触媒の創出により実用的なペプチド合成触媒となり得る。その実現に必要なgem-ジボロン類の官能基化に向け、既存法では困難な構造変換可能にする新規gem-ジボロン酸誘導体を見出しており、高活性ペプチド縮合触媒の創出に向けて引き続き検討を進める。